- BioRxiv Biochemistry
- BioRxiv Bioinformatics
- BioRxiv Biophysics
- BioRxiv Cancer Biology
- BioRxiv Pharmacology and Toxicology
- BioRxiv Systems Biology
- BioRxiv Zoology
- by Brandler, O. V., Tukhbatullin, A. R., Kapustina, S. Y., Tembotova, F. A., Puzachenko, A. Y.The greater blind mole rat S. microphthalmus is the only species that differs in the number of chromosomes (2n = 60) from the other species (2n = 62) of the genus Spalax. It also has the largest range among them. The intraspecific genetic and morphological variability of S. microphthalmus has been poorly studied so far. Previously, animals with 2n = 62 were found in the North Caucasus. This was interpreted as a manifestation of intraspecific polymorphism in greater blind mole […]
- by Hoyle, M., Rudge, J., Rallapalli, Y., Sarkar, A.Electroporation (EP) is one of the leading non-viral intracellular delivery methods used in various applications across research and cell therapy development and manufacturing. Currently widely used bulk EP methods, while they offer scalability, cost efficiency and simplicity, cannot be used for targeted or selective delivery to a defined subset of a input cell population. Here, we present a Microparticle-Enabled Selectively Permeabilizing Impedance Cytometer (ME-SPICy), a microfluidic single-cell EP platform that enables targeted EP of selected cell subpopulations based on their […]
- by Melamed, J. R., Muscat-Rivera, J., Kegel, M., Chaboub, L. S., Perez-Tremble, R., Bhalla, N. S., Ni, H., Sun, H., Weissman, D.The modularity of mRNA-lipid nanoparticle (mRNA-LNP) platforms has enabled their rapid adaptation from infectious disease vaccines to emerging applications in immune-mediated disorders. However, extending mRNA-LNPs to autoimmune and inflammatory diseases requires precise control over immune cell targeting and immunogenicity. Here, we systematically investigate how incorporating anionic lipids into LNPs modulates both immune cell tropism and innate immune activation. Using a library of 40 distinct LNP formulations, we demonstrate that anionic lipids enhance mRNA delivery to splenic dendritic cells, reduce early […]
- by Janowska, M. K., Racigh, V., Woods, C. N., Fornasari, M. S., Klevit, R. E.Zinc is an essential metal that supports diverse cellular functions. Zinc exerts its biological activity through protein binding, serving as catalytic cofactors and structural stabilizers of many enzymes, transcription factors, and ubiquitin E3 ligases, among others. Despite total cellular zinc concentrations reaching hundreds of micromolar, free zinc levels are tightly buffered. Elevated free zinc promotes mismetalation and protein aggregation. While zinc is redox-inert, its cysteine-based protein ligands are readily oxidized. Oxidative modification of cysteines leads to zinc dissociation and a […]
- by Ravikumar, V., Kulkarni, R., Maddox, A., Rao, A., Al-Holou, W.Glioblastoma (GBM) is the most common and lethal primary malignant tumor of the central nervous system. Advances in therapy are hindered by the complex intratumoral heterogeneity of GBM, where distinct malignant and non-malignant cellular states and interactions exist in spatially defined niches of the tumor microenvironment (TME), shaping both tumor behavior and treatment response. In this work, we define GBM biological reprogramming, TME recomposition, and cell-cell interactions in relation to spatially well defined Ivy Glioblastoma Atlas Project regions. Further, we […]
- by Saulay-Carret, M., Naveilhan, C., Corveleyn, X., Ramanoel, S.How do we translate information from a spatial map to action in our immediate surroundings? Despite the widespread use of various tools for orientation, from paper maps to GPS, this fundamental question remains unanswered in our understanding of human spatial navigation. To investigate this, we implemented a perspective-taking task in immersive virtual reality combined with mobile EEG, aiming to disentangle the neurocognitive processes involved. Thirty-eight young adults were presented with a virtual 2D map in which we manipulated both the […]
- by Jeneson, J. A. L., van den Berg-Faay, S., Hooijmans, M. T.We employed interleaved dynamic 1H magnetic resonance imaging (MRI) and 31P MR spectroscopy in combination with arm-cycling to investigate correlations of exercise hyperemia and muscle energetics in the triceps brachii (TB) muscle of the upper arm of healthy individuals. The parameter hyperemic slope (HS) determined from MRI acquisitions immediately after exercise was used as primary index of maximal TB oxygenation level in response to exercise. We found that HS tended to be inversely correlated with TB acidification during exercise (P […]
- by Vano, L. J., Sedlacik, J., Kaar, S. J., Rutigliano, G., Carr, R., Berry, A., Statton, B., Fazlollahi, A., Howes, O. D., McCutcheon, R. A.Background and Hypothesis Cognitive and negative symptoms in schizophrenia remain poorly treated. Iron dysregulation has been implicated as a potential mechanism underlying cognitive dysfunction and schizophrenia. While elevated postmortem iron in Brodmann areas 10-11 has been linked to schizophrenia, this has not been assessed in vivo. We therefore used iron-sensitive MRI to test whether cortical iron is elevated in individuals with schizophrenia compared to healthy controls. Study Design We acquired quantitative susceptibility mapping (QSM) MRI to measure magnetic susceptibility ({chi}), […]
- by Ren, Y., Cui, M. E., Herrmann, B.Within-situation disengagement – the mental withdrawal during conversations in acoustically challenging environments – is a common experience of older people with hearing difficulties. Yet, most research on the neural mechanisms of attentional disengagement from speech listening has focused on the distraction by one competing speaker, whereas within-situation disengagement is often characterized by distraction towards external visual stimuli or internal thoughts and occurs in situations with ambient, multi-talker background masking. Across three electroencephalography (EEG) experiments, the current study examined how disengagement […]
- by Rodriguez-Duboc, A., Racine, C., Basille-Dugay, M., Vaudry, D., Gonzalez, B., Burel, D.Apnea of prematurity (AOP) affects 50% of preterm infants causing intermittent hypoxia (IH), which can lead to long-term neurodevelopmental deficits. Cerebellar abnormalities have been observed in AOP but the relationship between vascular alterations and neural development remains unclear. This study investigates how IH affects cerebellar angiogenesis using a murine model of AOP. We developed an innovative 3D imaging workflow combining IMARIS and VesselVio software to quantitatively analyze cerebellar vascularization at different postnatal stages (P4, P8, P12, P21, and P70). We […]
- by Aldrich, J. C., Alman, S. M., Lee, S. E., Scheinfeld, A. R., Zhang, C. C., Pike, A. L., Bremner, F. C., Calderon, O., Goodwani, S., Ray, W. J., Gaudet, A. D.Spinal cord injury (SCI) causes devastating functional deficits, in part due to neuroinflammation, oxidative stress, and excitotoxicity that drive death of lesion-adjacent viable neurons. One signaling protein that promotes neuronal apoptosis and activates stress-responsive genes is dual leucine zipper kinase (DLK), which is a neuron-enriched kinase that responds to extracellular stress by activating the c-Jun N-terminal kinase (JNK) pathway. We hypothesized that SCI would robustly activate DLK signaling and that acute pharmacological inhibition of DLK would suppress JNK pathway activation, […]
- by Liu, S., Bradley, K., Tang, J. J., Kim, Y. A., Milosevic, A., Shaham, S.Astrocytic glia regulate brain assembly, synapse formation/activity, neuronal energetics, and brain metabolism. Gene programs driving astrocyte specification are only partly understood. Here, we use lineage-restricted single-cell RNA sequencing to uncover a two-phase developmental program for C. elegans CEPsh astrocyte differentiation. In phase one, newly generated astrocytes acquire common transcription profiles despite arising from lineally and transcriptionally distinct progenitors. Convergent differentiation is mediated by the distal-less transcription factor CEH-43. CEH-43 is expressed in astrocytes and their progenitors, binds conserved astrocyte-expressed genes, […]
- by Chen, L., Roy, A., David, G., Chiang, C.Cerebellar granule cells (GCs) are critical for motor and cognitive functions. Lineage tracing studies have identified a hierarchical developmental progression of GC neurogenesis, transitioning from Sox2+ stem-like cells to Atoh1+ rapidly proliferating granule cell precursors (GCPs), and ultimately to NeuN+ mature GCs. However, the molecular mechanisms governing these transitions remain poorly understood. In this study, we identified a transient, slow-cycling progenitor population defined by co-expression of Sox2 and Atoh1. We show that GC maturation depends critically on the repressive function […]
- by Tan, J., Luong, T., Paluzzi, J.-P. V.Neuropeptide Y-related signaling, consisting of various neuropeptides and their receptors including, for example, the mammalian neuropeptide Y (NPY), pancreatic polypeptide (PP), and peptide YY (PYY) families, along with neuropeptide Y-like peptides in insects, is evolutionarily conserved across vertebrates and invertebrate organisms. Vertebrate NPY is known as an important regulator of energy homeostasis and feeding behaviour, while studies on one NPY-associated signaling system in arthropods, known as RYamide, have mainly focused on functions regulating feeding-related behaviours. The current study aimed to […]
- by Allen, T., Peet, G., Gomez Wulschner, L., Oh, W. C., Macklin, W.Oligodendrocytes produce myelin, a lipid-rich membrane that wraps neuronal axons in the central nervous system to provide metabolic and trophic support and allow for saltatory conduction. Developmental myelination requires precisely timed and localized neuron-oligodendrocyte communication. In the mature brain, neuronal activity promotes oligodendrocyte precursor cell (OPC) proliferation and differentiation, but how OPCs respond to neuronal activity in early brain development, prior to the onset of myelination, is less well characterized. Here, we investigate how sensory-evoked and chemogenetically altered neuronal activity […]
- by Roura-Martinez, D., Ucha, M., Moreno-Fernandez, M., Castillo, C. A., Ballesteros-Yanez, I., Marcos, A., Ambrosio, E., Higuera-Matas, A. A.Stress is known to play a critical role in relapse to drug use as well as in food craving. Craving itself is a key determinant of relapse, and cue-induced drug craving has been shown to increase, or incubate, over time for certain drugs such as cocaine and nicotine, though this effect is less consistent for others such as opiates. However, the contribution of stress-related biochemical systems to the incubation of seeking has not yet been systematically examined in animal models, […]
- by Yee, D. M., Prater Fahey, M., Cheng, Z. M., Leng, X., Kim, J., Tarlow, M., Mundy, K., Nevins, S., Shenhav, A.Human motivation is fundamentally shaped by one's expectations of the reward they could earn for good performance or the punishment they would avoid for poor performance. However, the extent to which distinct brain regions are selectively associated with specific incentives and/or their corresponding influence on control strategy remains unclear. Using model-based fMRI and a novel multi-incentive control task, we observed distinct neural patterns by incentive valence, with ventral striatum and caudal subregion of dorsal anterior cingulate cortex showing greater sensitivity […]
- by Fujiwara, M., Naoki, H.Living systems maintain physiological variables such as temperature, blood pressure, and glucose within narrow ranges; a process known as homeostasis. Homeostasis involves not only reactive feedback but also anticipatory adjustments shaped by experience. Prior homeostatic reinforcement learning (HRL) models have provided a computational account of anticipatory regulation under homeostatic challenges. However, existing formulations lack mechanisms for gradual, trial-by-trial adjustment and for extinction learning. To address this issue, we developed a continuous HRL framework that enables trial-wise tuning of anticipatory regulation. […]
- by Stewart, E., Zielke, L. G., Guillaume, G., de Boer, A., Power, S. D., Ryan, T. J.Infantile amnesia, the inability to recall episodic memories formed during early childhood, is a hallmark of postnatal brain development. Yet the underlying mechanisms remain poorly understood. This work aimed to gain a better mechanistic understanding of infantile amnesia. Microglia, specialized macrophages of the central nervous system, are known to play an important role in synaptic refinement during postnatal development and have recently been implicated in memory related functions. Here, we identified microglia as key regulators of memory accessibility in infancy. […]
- by Lu, Z., Dowdle, L. T., Kay, K. N., Curtis, C. E.Neural theories of how the prefrontal cortex (PFC) supports working memory rely on evidence from decades of pioneering macaque research. In some respects, efforts to translate these animal models of working memory in human PFC using neuroimaging have largely failed. One possible explanation, before concluding key non-homologies between the species, is that previous neuroimaging studies used resolutions too coarse to be sensitive to intermixed distributions of neurons tuned to memorized features. To resolve this concern, we scanned human PFC at […]